22272-27-1Relevant articles and documents
Antimalarial N1, N3-Dialkyldioxonaphthoimidazoliums: Synthesis, Biological Activity, and Structure-activity Relationships
Ahenkorah, Stephen,Birkholtz, Lyn-Marie,Coertzen, Dina,Fridianto, Kevin,Go, Mei-Lin,Haynes, Richard K.,Lam, Yulin,Tan, Kevin S. W.,Tong, Jie Xin,Wittlin, Sergio
supporting information, p. 49 - 55 (2020/02/06)
Here we report the nanomolar potencies of N1,N3-dialkyldioxonaphthoimidazoliums against asexual forms of sensitive and resistant Plasmodium falciparum. Activity was dependent on the presence of the fused quinone-imidazolium entity and lipophilicity imparted by the N1/N3 alkyl residues on the scaffold. Gametocytocidal activity was also detected, with most members active at IC50 1 μM. A representative analog with good solubility, limited PAMPA permeability, and microsomal stability demonstrated oral efficacy on a humanized mouse model of P. falciparum.
Dioxonaphthoimidazoliums are Potent and Selective Rogue Stem Cell Clearing Agents with SOX2-Suppressing Properties
Ho, Si-Han Sherman,Ali, Azhar,Ng, Yi-Cheng,Lam, Kuen-Kuen Millie,Wang, Shu,Chan, Woon-Khiong,Chin, Tan-Min,Go, Mei-Lin
supporting information, p. 1944 - 1955 (2016/10/06)
Pluripotent stem cells are uniquely positioned for regenerative medicine, but their clinical potential can only be realized if their tumorigenic tendencies are decoupled from their pluripotent properties. Deploying small molecules to remove remnant undifferentiated pluripotent cells, which would otherwise transform into teratomas and teratomacarcinomas, offers several advantages over non-pharmacological methods. Dioxonapthoimidazolium YM155, a survivin suppressant, induced selective and potent cell death of undifferentiated stem cells. Herein, the structural requirements for stemotoxicity were investigated and found to be closely aligned with those essential for cytotoxicity in malignant cells. There was a critical reliance on the quinone and imidazolium moieties but a lesser dependence on ring substituents, which served mainly to fine-tune activity. Several potent analogues were identified which, like YM155, suppressed survivin and decreased SOX2 in stem cells. The decrease in SOX2 would cause an imbalance in pluripotent factors that could potentially prompt cells to differentiate and hence decrease the risk of aberrant teratoma formation. As phosphorylation of the NF-κB p50 subunit was also suppressed, the crosstalk between phospho-p50, SOX2, and survivin could implicate a causal role for NF-κB signaling in mediating the stem cell clearing properties of dioxonaphthoimidazoliums.
Molecular structures and biological evaluation of 2-chloro-3-(n-alkylamino) -1,4-napthoquinone derivatives as potent antifungal agents
Pawar, Omkar,Patekar, Ashwini,Khan, Ayesha,Kathawate, Laxmi,Haram, Santosh,Markad, Ganesh,Puranik, Vedavati,Salunke-Gawali, Sunita
, p. 68 - 74 (2014/01/06)
Derivatives of 2-chloro-3-(n-alkylamino)-1,4-naphthoquinone {n-alkyl: methyl; L-1, ethyl; L-2, propyl; L-3 and butyl; L-4} have been synthesized and characterized by elemental analysis, FT-IR, 1H NMR, UV-visible spectroscopy, LC-MS and single crystal X-ray diffraction studies. Antifungal activity of L-1 to L-4 has been evaluated against Candida tropicalis, Candida albicans and Cladosporium herbarum. The intramolecular hydrogen bonding affects the N-H vibrational frequency in L-2 (3273 cm-1). The single crystal X-ray structure reveal that L-1 and L-3 crystallizes in triclinic P-1, whereas L-2 crystallizes in orthorhombic Pca21 space group. An extensive intra and intermolecular hydrogen bonding interactions were observed in L-1 to L-3 which leads to molecular association. Intramolecular N-Ha?O hydrogen bonding were observed in L-1 to L-3. Moreover π-π stacking interactions were observed between the quinonoid rings of L-1 and L-3, however no such interactions were observed in L-2. An electrochemical study showed molecular association of L-1 to L-4 in DMSO solution. Compounds L-1 to L-4 were found to be potent antifungal agents against all the three strains, especially against C. tropicalis. Amongst these promising antifungal candidates, L-1 showed better activity compared to the clinically administered antifungal drug Amphotericin B and Nitrofurantoin with MIC = 1.25 μg ml-1 and MIC = 0.025 μg ml-1 respectively against C. albicans. Structure and activity relationship (SAR) study suggest a Log P value of ～2.0 and the cyclic voltammetry studies reveals additional chemical processes for L-1, which exhibits maximum activity against all fungal strains.
